title: Protein kinase C mediates increase of Ca2+ sensitivity for contraction by cholinoceptor partial agonist in ileal longitudinal muscle of guinea pig.
abstract: 1. Experiments were designed to study the roles of protein kinase C in carbachol- and pilocarpine-induced contraction and the increase in cytosolic Ca2+ concentration ([Ca2+]i) in guinea pig ileal longitudinal muscle. 2. The protein kinase C inhibitors, GF 109203X (10 microM), calphostin C (10 microM) and H-7 (10 microM), reduced the maximum of the concentration response curve produced by pilocarpine more effectively than that produced by carbachol. 3. The slopes of the regression lines between [Ca2+]i and tension development for pilocarpine and carbachol in tissues treated with GF 109203X were significantly gentler than those for untreated tissues. 4. The protein kinase C alpha- and beta 1 selective inhibitor Goe 6976 (1 microM) decreased both [Ca2+]i and contraction, but did not affect the slopes of the regression lines for pilocarpine and carbachol. 5. These results suggest that protein kinase C (both n- and/or a-type) plays an important role in the increase of Ca2+ sensitivity of the contractile element, and that pilocarpine mainly activates the protein kinase C-dependent pathways for contractile mechanisms in guinea pig ileal longitudinal muscle.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan. satoh@phar.toho-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Hayasaka
authors.forename: K
authors.initials: K
authors.lastname: Horiuchi
authors.forename: I
authors.initials: I
authors.lastname: Takayanagi
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D004396:Coloring Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011438:Propylbenzilylcholine Mustard / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology*; D012680:Sensitivity and Specificity
chemical_list: D002227:Carbazoles; D018678:Cholinergic Agents; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D011950:Receptors, Cholinergic; D010862:Pilocarpine; C081021:Go 6976; D011438:Propylbenzilylcholine Mustard; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002217:Carbachol; D011493:Protein Kinase C; C058819:calphostin C; C070515:bisindolylmaleimide I; D002118:Calcium; D016257:Fura-2